Invasion and Secondary Site Colonization as a Function of In Vitro Primary Tumor Matrix Stiffness: Breast to Bone Metastasis

Lekha Shah, Ayşe Latif, Kaye J. Williams, Elena Mancuso, Annalisa Tirella

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Abstract

Increased breast tissue stiffness is correlated with breast cancer risk and invasive cancer progression. However, its role in promoting bone metastasis, a major cause of mortality, is not yet understood. It is previously identified that the composition and stiffness of alginate-based hydrogels mimicking normal (1–2 kPa) and cancerous (6–10 kPa) breast tissue govern phenotype of breast cancer cells (including MDA-MB-231) in vitro. Here, to understand the causal effect of primary tumor stiffness on metastatic potential, a new breast-to-bone in vitro model is described. Together with alginate-gelatin hydrogels to mimic breast tissue, 3D printed biohybrid poly-caprolactone (PCL)-composite scaffolds, decellularized following bone-ECM deposition through Saos-2 engraftment, are used to mimic the bone tissue. It is reported that higher hydrogel stiffness results in the increased migration and invasion capacity of MDA-MB 231 cells. Interestingly, increased expression of osteolytic factors PTHrP and IL-6 is observed when MDA-MB-231 cells pre-conditioned in stiffer hydrogels (10 kPa, 3% w/v gelatin) colonize the bone/PCL scaffolds. The new breast-to-bone in vitro models herein described are designed with relevant tissue microenvironmental factors and could emerge as future non-animal technological platforms for monitoring metastatic processes and therapeutic efficacy.

Original languageEnglish
Pages (from-to)2201898
Number of pages1
JournalAdvanced Healthcare Materials
Volume12
Issue number3
Early online date9 Nov 2022
DOIs
Publication statusPublished (in print/issue) - Jan 2023

Bibliographical note

Publisher Copyright:
© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.

Keywords

  • Pharmaceutical Science
  • Biomedical Engineering
  • Biomaterials
  • invasive potential
  • breast-to-bone metastasis
  • in vitro models
  • matrix stiffness
  • alginate hydrogels
  • decellularized PCL scaffolds

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